Inducing Remission in Type 1 Diabetes With Alefacept (T1DAL)

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C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210,and 240 minutes post-meal. Results of the stimulated 2-hour (e.g., 120 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., AUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy primary endpoint.

Original Primary Outcome Measures ICMJE (submitted: August 22, 2009)

Difference in c-peptide production following a mixed meal tolerance test of subjects receiving alefacept, compared to those receiving placebo, at 12 months following enrollment. [ Time Frame: 12 months ]

C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210,and 240 minutes post-meal. Results of the stimulated 2-hour (e.g., 120 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., AUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy primary endpoint.

C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210,and 240 minutes post-meal. Results of the stimulated 2-hour (e.g., 120 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., AUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy primary endpoint.

Insulin Use in Units Per Kilogram Body Weight Per Day [ Time Frame: Baseline (Pre-treatment initiation), Week 52, and Week 104 ]

The need to use insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity.

Major Hypoglycemic Events Occurring From Randomization [ Time Frame: Baseline to Week 52 and Week 52 to Week 104 ]

Major hypoglycemic events are defined as a glucose concentration <55 mg/dL (grades 2-5, NCI-CTCAE version 3.0), or clinically: involving seizure(s) or involving loss of consciousness (coma), or requiring assistance from another individual in order to recover.

Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease. An HbA1c level of 5.6% or less is considered normal. HbA1c levels of 6.5% or higher is typical for individuals with Type 1 Diabetes Mellitus (T1DM). The closer HbA1c levels are to normal, the better controlled the disease is.

•Compared to baseline, change in C-peptide AUC from enrollment to AUC at 3, 6, 18 and 24 months. This change will be compared between subjects receiving alefacept and those receiving placebo. [ Time Frame: 3, 6, 18, 24mos ]

The purpose of this trial is to test whether a drug called alefacept will slow or halt destruction of the beta cells in the pancreas. If the destruction of the beta cells is stopped, the patients might be able to produce insulin on their own longer, which could stop or slow the progression of their type 1 diabetes.

This is a multi-center prospective, placebo-controlled, double-blind and randomized trial to investigate the ability of alefacept to protect residual beta cells from ongoing autoimmune destruction in adolescents and young adults with newly diagnosed Type 1 Diabetes Mellitus (T1DM).

Detailed Description

T1DM is an autoimmune disease that can emerge suddenly, causing dependence on insulin for life. This means that the immune system (the part of your body that helps fight infections) mistakenly attacks the cells in the pancreas that produce insulin (beta cells). As beta cells are destroyed, one's ability to produce insulin is decreased. Insulin helps keep blood glucose (sugar) levels normal.

For a period right after diagnosis, the pancreas is still able to make small amounts of insulin. Individuals with diabetes who have the ability to produce some of their own insulin may be able to achieve better blood sugar control than people who produce no insulin at all. Based on previous research, doctors think that giving medicines to affect the immune system soon after diagnosis may stop, delay, or decrease the destruction of beta cells, resulting in better glucose control. This can help prevent secondary complications of diabetes down the road.

Research has improved the outlook for T1DM over the last decade. Doctors are investigating, for example, how to save insulin-producing cells and extend the honeymoon period as long as possible.

Despite progress towards understanding the science behind T1DM, there remains a significant need to investigate alternative approaches to this disease in order to bring about long-term remission. For this reason, scientists are working hard to develop new treatments that can be given soon after diagnosis to preserve the remaining beta cells.

Currently there is no cure for T1DM; however, with new investigational medications and innovative clinical research studies, such as T1DAL, a new approach towards managing T1DM may be on the horizon.

Enrollees will receive weekly intramuscular injections of alefacept or placebo for two 12 week periods, with a 12-week pause between treatment intervals. This schedule or drug dosing may be altered due to the needs of the subject or at the discretion of the physician investigator.

Weekly intramuscular injections of a placebo saline solution of equal volume to the alefacept group for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.

Other Name: Inactive drug (pharmacologically)

Study Arms

Experimental: Alefacept

Subjects in this group receive weekly intramuscular injections of alefacept (15 mg) for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.

Intervention: Biological: Alefacept

Placebo Comparator: Placebo

Subjects in this group received weekly intramuscular injections of a placebo saline solution of equal volume to the alefacept group for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.

Participation in an investigational clinical trial within the last six weeks.

Sex/Gender

Sexes Eligible for Study:

All

Ages

12 Years to 35 Years (Child, Adult)

Accepts Healthy Volunteers

No

Contacts ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ICMJE

NCT00965458

Other Study ID Numbers ICMJE

DAIT ITN045AI

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Not Provided

IPD Sharing Statement

Plan to Share IPD:

Yes

Plan Description:

Participant level data access and additional relevant materials are available to the public in: 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal that makes data from the consortium's clinical trials publicly available.

Responsible Party

National Institute of Allergy and Infectious Diseases (NIAID)

Study Sponsor ICMJE

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators ICMJE

Immune Tolerance Network (ITN)

Juvenile Diabetes Research Foundation

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)